APP and major depressive disorder: In APP/PS1 mice, pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, decreased CRMP2 phosphorylation, improved energy metabolism, and mitigated motor coordination impairment and long term depression , but it is uncertain whether the effects were due to PPARγ activation or CRMP2 dephosphorylation [86,89].